Most researches associated with cell death have been focused on apoptosis of cells, also known as programmed cell death (PCD). With the discovery of the enzyme caspase, a number of pharmaceutical companies have promoted the development of drugs utilizing caspase inhibitors during the past 10 years. However, the current status is that no drugs have been approved by the FDA. This is because the apoptosis of cells is a cell death which occurs under physiological circumstances, and such a cell death may be due to the defense mechanism for maintaining homeostasis in the body. In contrast, necrosis is a cell death which mainly occurs under pathologic circumstances, and in most cases it is characterized by an accompanying inflammatory response. Necrosis has been known as an uncontrolled cell death for a long time, but according to recent research (Proskurykakov S Y et al., 2002, Biochemistry) typical diseases caused by necrosis include ischemic (e.g., myocardial infarction, stroke, renal infarction), neurodegenerative and inflammatory diseases. Since it is believed that necrosis is an uncontrolled, accidental cell death under pathologic circumstances, researches on the functional mechanism, molecular targets, signal transduction systems, etc. thereof have rarely been conducted. Therefore, there arises a compelling need to discover and develop necrosis-inhibiting substances for the treatment of ischemic, neurodegenerative, and inflammatory diseases which are caused by necrosis, and to elucidate biological, pathological causes of necrosis.
The indole derivatives according to the present invention have very useful structures from a medical viewpoint, and many publications have reported the research results with reference to these structures. Among the research results, the following are the most representative: International Publication No. WO 2006/112549 reported some indole derivatives having activity for glucokinase, International Publication No. WO 95/07276 reported indole derivatives useful as anti-tumor agents and as inhibitors against the production of cardiovascular system, and International Publication No. WO 2004/018428 reported indole derivatives useful as antibiotics.